POS1255 CLINICAL SIGNIFICANCE OF THE ANTI-NUCLEOLAR ORGANIZER REGION 90 ANTIBODIES (NOR90) IN SYSTEMIC SCLEROSIS: A EUROPEAN SCLERODERMA TRIALS AND RESEARCH (EUSTAR) ANALYSIS
Authors: A. Dima, A. Garaiman, M. Vonk, B. Kersten, R. Bečvář, M. Tomcik, A. M. Hoffmann-Vold, I. Castellví, J. L. Tandaipan, M. Brzosko, M. Milchert, D. Krasowska, M. Michalska-Jakubus, P. Airò, M. Matucci-Cerinic, C. Bruni, M. Iudici, J. Distler, A. M. Gheorghiu, H. Poormoghim, F. Motta, M. De Santis, M. Parvu, O. Distler, C. Mihai
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) identified in up to 6% of patients with systemic sclerosis (SSc). However, due to the small number of available studies, the clinical relevance of NOR90 in SSc remains uncertain. <h3>Objectives</h3> To analyze clinical associations of NOR90 in patients with SSc in a multicentric cohort. <h3>Methods</h3> Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) group database, with additional information on NOR90 provided by participating centers (EUSTAR project CP105). NOR90 was tested using immunoassays. Differences between patients with and without NOR90 were assessed using the U Mann-Whitney and the Chi-square test, and clinical associations were tested using regression models. <h3>Results</h3> Overall, 1318 patients with SSc were included (mean age 58.3±13.7 years, 81.3% female), of whom 44 (3.3%) were positive for NOR90, that were also positive for other SSc-specific antibodies: anti-topoisomerase I (20.5%), anti-centromere (42.9%), and anti-RNA polymerase III (12.5%). The demographic and clinical data of NOR90-positive and -negative patients are displayed in Table 1. There was no difference in the presence of severe organ manifestations including interstitial lung disease, pulmonary hypertension, and renal crisis, but NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal symptoms compared to NOR90-negative patients. In multivariable regression models adjusted for the presence of the most frequent SSc-specific antibodies, NOR90 remained significantly associated with lower mRSS and with less frequent gastrointestinal symptoms (Figure 1). <h3>Conclusion</h3> To the best of our knowledge, this is the largest SSc cohort tested for NOR90 so far. Apart from negative associations with skin fibrosis and GI symptoms, which should be analyzed in further studies, we did not find any significant association of NOR90 with SSc-associated organ/ system involvement. However, these patients had a considerable prevalence of severe organ manifestations and should therefore be carefully evaluated. <h3>Acknowledgements</h3> Alina Dima, Alexandru Garaiman, and Madelon Vonk share equal contribution. <h3>Disclosure of Interests</h3> Alina Dima Grant/research support from: EULAR Scientific training grant for young fellow, Alexandru Garaiman: None declared, Madelon Vonk Speakers bureau: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis, Consultant of: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis, Brigit Kersten: None declared, Radim Bečvář: None declared, Michal Tomcik: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp &amp; Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp &amp; Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Jannsen, Ivan Castellví Speakers bureau: Boehringer, Janssen-Cilag, BMS, Roche, UCB., Consultant of: Boehringer, Janssen-Cilag, Topandur, Jose Luis Tandaipan: None declared, Marek Brzosko: None declared, Marcin Milchert: None declared, Dorota Krasowska Speakers bureau: Novartis, Abbvie, Elli Lilly, Consultant of: Boehringer Ingelheim, Novartis, Janssen, Małgorzata Michalska-Jakubus: None declared, Paolo Airò Speakers bureau: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag, Consultant of: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag, Marco Matucci-Cerinic Speakers bureau: Biogen, Sandoz, Boehringer, Lilly, Galapagos, Grant/research support from: MSD, Janssen, Cosimo Bruni Speakers bureau: Eli Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), AbbVie, Michele Iudici: None declared, Joerg Distler: None declared, Ana Maria Gheorghiu Speakers bureau: Sandoz, Boehringer Ingelheim, Ewopharma, Consultant of: Boehringer Ingelheim, Hadi Poormoghim: None declared, Francesca Motta Consultant of: Thermo Fisher, Maria De Santis: None declared, Magda Parvu: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Consultant of: Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Carina Mihai Speakers bureau: from Boehringer Ingelheim, Janssen, MED Talks Switzerland, Mepha, and PlayToKnow AG, Grant/research support from: Boehringer Ingelheim, Roche.